In vitro activity of hydroxychloroquine in combination with antibiotics against intracellular uropathogenic Escherichia coli

Abstract

BackgroundTwo pathophysiological concepts may explain recurrent UTI: a reinfection by a bacterial strain from the digestive microbiota or a relapse from Escherichia coli persisting within the superficial urothelial cells as intracellular bacterial communities (IBC). Hydroxychloroquine (HCQ)-antibiotic combination is effective against intracellular adherent-invasive E. coli isolated from patients with Crohns disease. We hypothesized that HCQ may enhanced antibiotic efficacy against E. coli IBC. MethodsUTI89 reference strain and two clinical E. coli strains forming IBCs (VITALE#2157, VITALE#2206) were used in this study. MIC, MBC and time killing curves (4xMIC) were performed for AZYTHROMYCIN (AZT), CIPROFLOXACIN (CIP), DOXYCYCLINE (DC), FOSFMOMYCIN (FF) and HCQ. In vitro activity of antibiotics alone and combined with HCQ was evaluated on intracellular bacterial survival assay using a model of urothelium cells (HTB-9). ResultsTime-killing curves showed that CIP has a bactericidal activity at H6 (-4.6 log10 CFU/mL) with regrowth at H24 against 2157, and a bactericidal activity at H6 without regrowth at H24 against 2206 (-3.3 log10 CFU/mL) and UTI89 (-3.4 log10 CFU/mL); DC, AZT and FF demonstrated bacteriostatic activity at H24 regardless of the strain. We observed a significant decrease in the number of intracellular bacteria at H42 with CIP (-1.83 log10 / 106 cells). DC, FF, and AZT exposure did not reduce IBC formation at H42 (P>0.05). IBC formation after HCQ-antibiotic combination exposure was not significantly different (P>0.05) from antibiotic exposure alone, regardless of the antibiotic or strain studied. ConclusionsIn conclusion, HCQ exposure does not enhance antibiotics activity against intracellular uropathogenic E. coli. HighlightsO_LIUsing an in vitro model of superficial urothelium monolayer, we observed a significant decrease in intracellular uropathogenic Escherichia coli in response to ciprofloxacin exposure. C_LIO_LIHydroxychloroquine exposure does not enhance antibiotics activity against intracellular uropathogenic Escherichia coli. C_LI